法沃斯基重排 Favorskii rearrangement — 定义、原理与由来

定义Definition

法沃斯基重排是 α-卤代酮在碱（醇钠、氢氧化物或胺）作用下重排为羧酸衍生物（酯、酸或酰胺）的反应；环状 α-卤代酮重排时发生缩环。

The Favorskii rearrangement converts an α-halo ketone, under base (alkoxide, hydroxide or amine), into a carboxylic acid derivative (ester, acid or amide); cyclic α-halo ketones undergo ring contraction.

机理Mechanism

碱夺取卤素另一侧的 α′-H 生成烯醇负离子，烯醇碳进攻带卤素的碳，分子内取代形成环丙酮中间体。亲核试剂进攻环丙酮羰基，三元环向能生成更稳定碳负离子的一侧开环，质子化得产物。

Base removes the α′-H on the other side of the carbonyl to form an enolate, which displaces the halide intramolecularly to give a cyclopropanone intermediate. The nucleophile adds to the cyclopropanone carbonyl, the ring opens toward the more stable carbanion, and protonation gives the product.

由来Origin

俄国化学家阿列克谢·法沃斯基于 1894 年报道。环丙酮中间体的机理在 20 世纪中叶由同位素标记实验确立。

Reported by the Russian chemist Alexei Favorskii in 1894; the cyclopropanone mechanism was established by isotopic labelling in the mid-twentieth century.

应用Applications

缩环特性使其成为合成小环、张力化合物的方法，例如由 2-氯环己酮得到环戊烷甲酸甲酯；伊顿合成立方烷的路线中也用到了双重法沃斯基缩环。

Its ring contraction makes it useful for strained rings: 2-chlorocyclohexanone gives methyl cyclopentanecarboxylate, and Eaton's cubane synthesis uses a double Favorskii contraction.

反应Reactions

R–CO–CHX–R′ + RO⁻ ⟶ 重排的酯 R(R′)CH–COOR + X⁻R–CO–CHX–R′ + RO⁻ ⟶ R(R′)CH–COOR + X⁻

醇钠/醇、NaOH/水或胺，常温或加热

Alkoxide/alcohol, NaOH/water or amines, room temperature or heating

α′-H 脱质子生成烯醇负离子。
Deprotonation at α′ gives an enolate.
分子内 SN2 形成环丙酮。
Intramolecular SN2 forms a cyclopropanone.
亲核试剂加成到羰基，开环生成较稳定的碳负离子。
Nucleophilic addition to the carbonyl and ring opening to the more stable carbanion.
质子化得到羧酸衍生物。
Protonation gives the acid derivative.

2-氯环己酮 + NaOMe ⟶ 环戊烷甲酸甲酯2-Cyclohexanone + NaOMe ⟶ PentaneFormic acid

经典的缩环例子。

The classic ring contraction.

年表Timeline

1894
法沃斯基报道该重排
Favorskii reports the rearrangement
1964
伊顿与科尔用法沃斯基缩环合成立方烷
Eaton and Cole use Favorskii contractions to make cubane

法沃斯基重排Favorskii rearrangement